Haploidentical Stem Cell Transplantation in Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00790413
• Other study ID #: 385/2005
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: August 2005
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2021
• Source: Lund University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell transplantation (haploSCT) followed by low-dose donor lymphocyte infusions will be piloted. The use of the isotope is aimed to decrease pre-transplant tumour burden. Reduced intensity conditioning containing Fludarabine, Thiotepa and Melfalan will enable sustained engraftment as well as will serve as additional anti-tumor treatment. A prompt natural killer (NK)-cell mediated tumour control may be achieved by haploidentical stem cell transplantation. The investigators hypothesize that tumour cells potentially evading NK-cell mediated immunity may be targeted by infused donor T-cells and eliminated by either MHC-dependent manner or through a bystander effect. The possible graft versus tumor effect will be evaluated in children with therapy resistant neuroblastoma.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 21 Years

Eligibility

Inclusion Criteria:

• Refractory neuroblastoma (any chemo/radiosensitive stable disease)

• Relapse incl. autologous HSCT 3 m earlier

• Primary induction failure

• Cardiac output SF =25%

• Creatinine clearance =40 cc/min/1.73 m2

• Performance score of =50% (Lansky or Karnofsky)

• Available haploidentical family donor, aged =18 yrs, HIV-neg

Exclusion Criteria:

• Rapidly progressive disease

• Pregnancy

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• iodine I 131 metaiodobenzylguanidine

• Fludarabine

• Thiotepa

Procedure:
• T-cell depletion

• Haploidentical stem cell transplantation

• Donor Lymphocyte Infusion

Drug:
• Rituximab

Procedure:
• Co-transplantation of mesenchymal stem cells

Locations

Country	Name	City	State
Sweden	Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation	Lund

Sponsors (1)

Lead Sponsor	Collaborator
Lund University Hospital

Country where clinical trial is conducted

Sweden, 

References & Publications (8)

Illhardt T, Toporski J, Feuchtinger T, Turkiewicz D, Teltschik HM, Ebinger M, Schwarze CP, Holzer U, Lode HN, Albert MH, Gruhn B, Urban C, Dykes JH, Teuffel O, Schumm M, Handgretinger R, Lang P. Haploidentical Stem Cell Transplantation for Refractory/Rela — View Citation

Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura-Yagi K, Sakata N, Yasui M, Okamura T, Kawa K. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant. 2003 Jul;32(1):103-6. — View Citation

Lang P, Pfeiffer M, Müller I, Schumm M, Ebinger M, Koscielniak E, Feuchtinger T, Föll J, Martin D, Handgretinger R. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr. 2006 Nov-Dec;218(6):321-6. — View Citation

Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JM. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006 Jan 20;24(3):500-6. — View Citation

Neal ZC, Imboden M, Rakhmilevich AL, Kim KM, Hank JA, Surfus J, Dixon JR, Lode HN, Reisfeld RA, Gillies SD, Sondel PM. NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother. 2004 Jan;53(1):41-52. Epub 2003 Sep 18. — View Citation

Prigione I, Corrias MV, Airoldi I, Raffaghello L, Morandi F, Bocca P, Cocco C, Ferrone S, Pistoia V. Immunogenicity of human neuroblastoma. Ann N Y Acad Sci. 2004 Dec;1028:69-80. Review. — View Citation

Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V. Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene. 2005 Jul 7;24(29):4634-44. — View Citation

Toporski J, Garkavij M, Tennvall J, Ora I, Gleisner KS, Dykes JH, Lenhoff S, Juliusson G, Scheding S, Turkiewicz D, Békássy AN. High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Engraftment rate		day 100
Secondary	Overall survival		1 year
Secondary	Immunological reconstitution		day 100
Secondary	Incidence of acute graft versus host disease		day 100